Increased Frequency of CD4+ Follicular Helper T and CD8+ Follicular T Cells in Human Lymph Node Biopsies during the Earliest Stages of Rheumatoid Arthritis.
Authors
Ramwadhdoebe, Tamara H
Hähnlein, Janine S
van Kuijk, Bo
Smits, Noortje
van Lienden, Krijn P
Maas, Mario
Gerlag, Daniëlle M
de Vries, Niek
Publication Date
2022-03-24Journal Title
Cells
ISSN
2073-4409
Publisher
MDPI AG
Volume
11
Issue
7
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Anang, D. C., Ramwadhdoebe, T. H., Hähnlein, J. S., van Kuijk, B., Smits, N., van Lienden, K. P., Maas, M., et al. (2022). Increased Frequency of CD4+ Follicular Helper T and CD8+ Follicular T Cells in Human Lymph Node Biopsies during the Earliest Stages of Rheumatoid Arthritis.. Cells, 11 (7) https://doi.org/10.3390/cells11071104
Abstract
Follicular T helper cells (Tfh cells) provide key B-cell help and are essential in germinal center formation and (auto) antibody generation. To gain more insight into their role during the earliest phase of rheumatoid arthritis (RA), we analyzed their frequencies, phenotypes, and cytokine profiles in peripheral blood and lymph node biopsies of healthy controls (HCs), autoantibody-positive individuals at risk for developing RA (RA-risk individuals), and early RA patients. Subsequently, we confirmed their presence in lymph nodes and synovial tissue of RA patients using immunofluorescence microscopy. In the blood, the frequency of Tfh cells did not differ between study groups. In lymphoid and synovial tissues, Tfh cells were localized in B-cell areas, and their frequency correlated with the frequency of CD19+ B cells. Compared to lymphoid tissues of healthy controls, those of RA patients and RA-risk individuals showed more CD19+ B cells, CD4+CXCR5+ follicular helper T cells, and CD8+CXCR5+ follicular T cells. These Tfh cells produced less IL-21 upon ex vivo stimulation. These findings suggest that Tfh cells may present a novel rationale for therapeutic targeting during the preclinical stage of RA to prevent further disease progression.
Keywords
rheumatoid arthritis, lymph nodes, T lymphocytes, B lymphocytes, follicular T helper cells
Sponsorship
Innovative Medicines Initiative - BeTheCure (115142, 765158, FP7-HEALTH-F2-2012-305549, 11-1-308, 916.12.109)
Identifiers
External DOI: https://doi.org/10.3390/cells11071104
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335436
Rights
Licence:
https://creativecommons.org/licenses/by/4.0/
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